Molecular Basis of Sickling: The aggregation of sickle hemoglobin will be studied by measurements of viscosity and the solubility of hemoglobin S in equilibrium with sickle hemoglobin gel. These techniques will be used to evaluate the interaction of S and non S hemoglobins and to determine the role of the asymmetrical hybrid (such as Alpha 2 Beta s Beta a) in the formation of the sickle polymer. The effect of tonic strength and CO2 on sickling will also be determined. Evaluation of New Hemoglobin Variants: Structural and functional studies will be done on a limited number of hemoglobin variants. We hope to adapt isoelectric focusing on polyacrylamide gels to the analysis of globin peptides. Variants with abnormal oxygen binding or decreased stability will be of particular interest. The interaction of selected variants with hemoglobin S will be tested.